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Antenatal Steroids and Cord Blood T-cell Glucocorticoid Receptor DNA Methylation and Exon 1 Splicing

Jeanette R Carpenter1, Kathleen A Jablonski2, Jordan Koncinsky3

  • 1Obstetrics & Gynecology, University of Utah, Salt Lake City, UT, USA.

Reproductive Sciences (Thousand Oaks, Calif.)
|February 11, 2022
PubMed

Insights

Antenatal betamethasone (BMZ) alters neonatal immune cell proportions, increasing granulocytes and decreasing lymphocytes. However, BMZ exposure did not affect glucocorticoid receptor (GR) gene methylation or exon 1 transcript levels in cord blood T-cells.

Area of Science:

  • Immunology
  • Neonatal Medicine
  • Molecular Biology

Background:

  • Antenatal glucocorticoids like betamethasone (BMZ) improve preterm infant respiratory outcomes.
  • Concerns exist regarding potential long-term immune programming effects of antenatal BMZ.
  • The glucocorticoid receptor (GR) gene is a key mediator of glucocorticoid action.

Purpose of the Study:

  • To investigate if antenatal BMZ exposure alters cord blood immune cell composition.
  • To determine if antenatal BMZ is associated with changes in DNA methylation of the GR gene promoter.
  • To examine if antenatal BMZ affects the expression of alternatively spliced GR exon 1 transcripts in cord blood CD4+ T-cells.

Main Methods:

  • Analysis of cord blood samples from 51 infants (27 BMZ, 24 placebo) in the Antenatal Late Preterm Steroids Trial.
  • Comparison of leukocyte proportions between BMZ-exposed and placebo groups.
  • Assessment of DNA methylation at GR promoter CpG sites and GR mRNA exon 1 variant expression in CD4+ T-cells.

Main Results:

  • BMZ exposure was linked to a significant increase in granulocytes (51.6% vs. 44.7%, p=0.03) and a decrease in lymphocytes (36.8% vs. 43.0%, p=0.04) as a percentage of total leukocytes.
  • No significant differences were observed in GR promoter DNA methylation levels between the BMZ and placebo groups.
  • Expression levels of GR exon 1 transcripts did not differ between infants exposed to BMZ and those in the placebo group.

Conclusions:

  • Antenatal betamethasone administration is associated with alterations in cord blood leukocyte composition.
  • Despite immune cell proportion changes, antenatal BMZ did not induce detectable alterations in GR gene methylation or alternative exon 1 transcript expression in cord blood CD4+ T-cells.
  • Further research is needed to fully understand the long-term immunomodulatory programming effects of antenatal glucocorticoids.

Keywords:
BetamethasoneEpigeneticsProgramming

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